Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.

The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown. We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19. This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1β, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1β (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes. The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes. The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718.

Fernandes AL ，Murai IH ，Reis BZ ，Sales LP ，Santos MD ，Pinto AJ ，Goessler KF ，Duran CSC ，Silva CBR ，Franco AS ，Macedo MB ，Dalmolin HHH ，Baggio J ，Balbi GGM ，Antonangelo L ，Caparbo VF ，Gualano B ，Pereira RMR ... -  《-》

Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial.

Murai IH ，Fernandes AL ，Sales LP ，Pinto AJ ，Goessler KF ，Duran CSC ，Silva CBR ，Franco AS ，Macedo MB ，Dalmolin HHH ，Baggio J ，Balbi GGM ，Reis BZ ，Antonangelo L ，Caparbo VF ，Gualano B ，Pereira RMR ... -  《-》

Effect of vitamin D(3) on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19.

To investigate the effect of a single oral dose of 200,000 IU of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19. This is a post-hoc, exploratory analysis from a double-blind, placebo-controlled, randomized clinical trial performed in two centers in Sao Paulo, Brazil. Hospitalized patients with COVID-19 were randomly assigned to receive either vitamin D3 (n = 97) or placebo (n = 97). In this post-hoc analysis, the endpoints were titers and frequency of anti-β2-Glycoprotein-I (aβ2-GP) and Anticardiolipin (aCL) antibodies [Immunoglobulin G, M and A (IgG, IgM and IgA)]. Overall mean (SD) age was 55.3 (13.9) years, Body Mass Index (BMI) was 32.2 (7.1 kg/m2), and 106 participants (54.6 %) were male. There was a significant group by time interaction (p = 0.046) for frequency of aCL IgG, with increased values from baseline to discharge in the placebo group [n (%), from 13 (13.4) to 25 (25.8)] compared to the vitamin D3 [from 25 (25.8) to 29 (29.9)]. However, the frequency of aCL IgG did not change between the groups on discharge. No significant differences between vitamin D3 and placebo groups were found for any other autoantibodies. These findings do not support the use of a single oral dose of 200,000 IU of vitamin D3 to modulate autoantibodies in hospitalized patients with moderate to severe COVID-19.

Sales LP ，Souza LVB ，Fernandes AL ，Murai IH ，Santos MD ，Vendramini MBG ，Oliveira RM ，Figueiredo CP ，Caparbo VF ，Gualano B ，Pereira RMR ，in memoriam ... -  《-》

Persistent or new symptoms 1 year after a single high dose of vitamin D(3) in patients with moderate to severe COVID-19.

The aim of this study was to investigate the reported persistent or new symptoms 1 year after a single dose of 200,000 IU of vitamin D3 and hospitalization in patients with moderate to severe COVID-19. This is a post-hoc, exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial from two hospitals in São Paulo, Brazil, registered in ClinicalTrials.gov, NCT04449718. Discharged patients were followed for up to 1 year and evaluated by telephone interviews at 6 and 12 months. The primary and secondary outcomes were previously published. These post-hoc exploratory secondary outcomes are the persistent or new symptoms and quality of life (QoL) at the post-viral stage of COVID-19. Generalized estimating equations (GEE) for repeated measures with Bonferroni's adjustment were used for testing outcomes. Between 2 June and 27 August 2020, we randomized 240 patients of which 144 were included in this study [the vitamin D3 (n = 71) or placebo (n = 73) group]. The mean (SD) age was 54.3 (13.1) years, and body mass index (BMI) was 32.4 (6.5) kg/m2. Fever demonstrated a significant main effect of time (P < 0.001) with a reduction from baseline to 6 (52-0) and 12 months (52-0). No significant differences between groups were observed for fever, cough, fatigue, fever, myalgia, joint pain, runny nose, nasal congestion, sore throat, hypertension, diabetes, cardiovascular disease, rheumatic disease, asthma, chronic obstructive pulmonary, chronic kidney disease, QoL, and new or persistent symptoms up to 1-year of follow-up. The findings do not support the use of 200,000 IU of vitamin D3 compared to placebo for the management of persistence or new symptoms, and QoL reported by moderate to severe patients after hospitalization for COVID-19.

Fernandes AL ，Sales LP ，Santos MD ，Caparbo VF ，Murai IH ，Pereira RMR ... -  《-》

A whole blood test to measure SARS-CoV-2-specific response in COVID-19 patients.

To examine whether specific T-cell-responses to SARS-CoV-2 peptides can be detected in COVID-19 using a whole-blood experimental setting, which may be further explored as a potential diagnostic tool. We evaluated interferon (IFN)-γ levels after stimulating whole-blood with spike and remainder-antigens peptides megapools (MP) derived from SARS-CoV-2 sequences; interleukin (IL)-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, eotaxin, basic fibroblast growth factor (FGF), granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), IFN-γ, Interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-1β, Platelet-derived growth factor (PDGF), RANTES (regulated on activation, normal T cell expressed and secreted), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF) were also evaluated. IFN-γ-response to spike and remainder-antigens MPs was significantly increased in 35 COVID-19 patients compared with 29 'no COVID-19' individuals (medians spike-MP: 0.26 vs 0, p = 0.0002; medians remainder-antigens-MP: 0.07 vs 0.02; p = 0.02). This response was detected independently of patients' clinical parameters. IFN-γ-response to SARS-CoV-2-unrelated antigens cytomegalovirus (CMV) and Staphylococcal Enterotoxin B (SEB) was similar in COVID-19 compared with 'no COVID-19' individuals (median CMV: 3.46 vs 5.28, p = 0.16; median SEB: 12.68 vs 15.05; p = 0.1). In response to spike-MPs in COVID-19- compared with 'no COVID-19' -individuals, we found significant higher median of IL-2 (50.08 vs 0, p = 0.0018), IFN-γ (90.16 vs 0, p = 0.01), IL-4 (0.52 vs 0, p = 0.03), IL-13 (0.84 vs 0, p = 0.007) and MCP-1 (4602 vs 359.2, p = 0.05). Immune response to SARS-CoV-2 peptides in a whole-blood assay is associated with COVID-19 and it is characterized by both Th1 and Th2 profile. This experimental approach may be useful for developing new T-cell based diagnostic tests for disease and vaccine settings.

Petrone L ，Petruccioli E ，Vanini V ，Cuzzi G ，Najafi Fard S ，Alonzi T ，Castilletti C ，Palmieri F ，Gualano G ，Vittozzi P ，Nicastri E ，Lepore L ，Antinori A ，Vergori A ，Caccamo N ，Cantini F ，Girardi E ，Ippolito G ，Grifoni A ，Goletti D ... -  《-》